THE
FIELD
Historically, research in the pharmaceutical sciences and in the
broad area of genetics has developed concurrently, but with little
interaction. The goal of research in the pharmaceutical sciences
is to optimize drug therapy and to produce effective drug products
that are associated with a minimum of adverse effects. The goal
of research in human genetics is to understand how genetic information
defines how a human develops and how mutations lead to dysfunction.
For years, it has been recognized that there is considerable variability
in the response of individuals to given drugs, which is related
to variability in the pharmacokinetics or pharmacodynamics. This
variability may be a result of genetic variation in the effector
proteins (e.g., enzymes, transporters, receptors) that are involved
in drug response. There are a number of examples of genetic variation
in enzymes resulting in variability in drug response.
Although
these classical examples invoke an appreciation of the genetic
contributions to drug response, the techniques to seek out further
examples of these connections have only recently become available.
Research in human genetics has focused primarily on the study
of rare diseases and has included more recent studies in which
the responsible genes have been identified through molecular cloning
methods. Recently, there has been a revolution in the field of
human genetics, driven primarily by the Human Genome Project.
With the identification and mapping of nearly 100,000 genes, a
major impact on diagnosis and treatment of human disease is anticipated.
The impact on the pharmaceutical sciences will be enormous with
the development of an understanding of the multiple genetic polymorphisms
that cause variation in drug response.
Enormous excitement
exists in the fields of pharmaceutical sciences and human genetics,
as people in each of these historically separate areas realize
that understanding genetic contributions to drug response is an
exciting frontier for both groups. Examples are compelling:
(a) identification
of better candidate drugs during pre-clinical drug development;
(b) better definition of how people respond to a drug (for example,
metabolize it), which will inform clinical trials and lead to
greater success rates for drug approval;
(c) better efficacy for therapeutically available drugs;
(d) identification of genetic basis for adverse drug response,
which will be informative during clinical trials and in post-marketing
surveillance.
